oritavancin and Soft-Tissue-Infections

Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals.. We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and to each other for the treatment of complicated SSTIs (cSSTI). A search for randomized controlled trials (RCTs) was conducted in Medline, Embase and the Cochrane Central Register of Controlled Trials. We also developed a model to evaluate the costs associated with dalbavancin and oritavancin from the third-party payer perspective.. Seven RCTs met the inclusion criteria. Network meta-analyses suggested that the clinical response to telavancin, dalbavancin and oritavancin was similar to standard care (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.90-1.33; OR 0.78, 95% CI 0.52-1.18; and OR 1.06, 95% CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; 95% CI 0.85-2.18), oritavancin and telavancin (OR 0.98; 95% CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; 95% CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; 95% CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; 95% CI 0.45-0.76) and oritavancin (OR 0.71; 95% CI 0.55-0.92). Studies were of high quality overall. Our cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care under baseline assumptions and many scenarios evaluated. The use of dalbavancin could save third-party payers $1442 to $4803 per cSSTI, while the use of oritavancin could save $3571 to $6932 per cSSTI.. Dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care in well-designed RCTs and result in cost savings when standard care is treatment that covers MRSA.

Topics: Anti-Bacterial Agents; Costs and Cost Analysis; Drug Therapy; Glycopeptides; Humans; Lipoglycopeptides; Network Meta-Analysis; Skin Diseases, Bacterial; Soft Tissue Infections; Teicoplanin

Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Ceftaroline; Cephalosporins; Daptomycin; Female; Fluoroquinolones; Glycopeptides; Hospitalization; Humans; Iatrogenic Disease; Internal Medicine; Linezolid; Lipoglycopeptides; Male; Minocycline; Oxazolidinones; Skin Diseases, Infectious; Soft Tissue Infections; Teicoplanin; Tigecycline; Vancomycin

Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can 'nudge' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy. We review five new antimicrobials recently FDA-approved for use in drug-resistant infections: dalbavancin, oritavancin, ceftaroline, ceftolozane-tazobactam, and ceftazidime-avibactam.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Administration Schedule; Drug Approval; Drug Combinations; Drug Resistance, Microbial; Glycopeptides; Humans; Lipoglycopeptides; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Soft Tissue Infections; Teicoplanin; United States; United States Food and Drug Administration

Oritavancin is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This antibiotic has multiple mechanisms of action including inhibiting peptidoglycan cell wall synthesis and disrupting bacterial cell membrane, leading to cell death. Oritavancin is highly active against common gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. The drug is administered as a single intravenous dose of 1200 mg over 3 hours in adult patients, and because of its terminal half-life of 393 hours, repeat dosing is not required in the treatment of ABSSIs. There is a very slow elimination from tissue sites, and no dosing adjustments are required for renal or hepatic insufficiency. Two clinical trials have demonstrated noninferiority compared with vancomycin in the treatment of ABSSSIs. Other than liver enzyme elevation and the occurrence of osteomyelitis, oritavancin has been associated with adverse events similar to those of vancomycin in follow-up for up to 60 days. Patients should be monitored for osteomyelitis and alternate therapy given in the case of confirmed or suspected osteomyelitis. Although oritavancin is an attractive antibiotic to consider in the outpatient area, its efficacy and safety in the treatment of other sites of infection are yet to be established.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Enzymes; Glycopeptides; Gram-Positive Bacterial Infections; Half-Life; Humans; Lipoglycopeptides; Liver; Osteomyelitis; Skin Diseases, Bacterial; Soft Tissue Infections

There is a choice of anti-MRSA antibiotic available with proven efficacy in the treatment of complicated skin and skin structure infection (cSSSI). Additional anti-MRSA antibiotics are in development, which have the potential to influence how such infections are managed. The emergence of resistance to current anti-MRSA agents, toxicity, and general lack of oral agents with proven efficacy for deep seated infection justify the development of new agents. However, there is a relative dearth of information specific to patients with orthopaedic-related infection. Combination therapy is often used in these patients, although there is a paucity of controlled trial data to support particular antibiotic combinations. As the choice of anti-MRSA agents increases, so does the need to identify which are best for the large variety of infections included in the group of cSSSIs. This is particular true for infections occurring in orthopaedic patients where poorly vascularised tissue, trauma or implanted prosthetic material, pose specific challenges.

Topics: Aminoglycosides; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Teicoplanin

Oritavancin is a lipoglycopeptide antibiotic with activity against aerobic and anaerobic Gram-positive bacteria. Oritavancin separates itself from other glycopeptides through its potent in vitro activity against resistant isolates of Staphylococcus aureus, Enterococcus spp. and Streptococcus spp. Oritavancin possesses a long half-life that should allow, at maximum, once-daily dosing. Currently, oritavancin has completed two Phase III trials and one Phase II trial for the treatment of complicated skin and skin structure infections, and two Phase II trials for the treatment of Gram-positive bacteremia. In all instances, oritavancin displayed favorable outcomes and was noninferior to comparator agents (vancomycin followed by oral cephalexin) when a comparison was made. Further studies are necessary to fully characterize dose and clinical role.

Topics: Anti-Bacterial Agents; Bacteremia; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Half-Life; Humans; Lipoglycopeptides; Soft Tissue Infections; Treatment Outcome

Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment.. In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) ≥20% reduction in lesion area at 48-72 hours.. A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining ≥20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups.. A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs. Clinical Trials Registration. NCT01252732.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Double-Blind Method; Female; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Male; Middle Aged; Skin Diseases, Bacterial; Soft Tissue Infections; Treatment Outcome; Vancomycin; Young Adult

Topics: Anti-Bacterial Agents; Glycopeptides; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Neoplasms; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Emergency Service, Hospital; Glycopeptides; Humans; Lipoglycopeptides; Skin Diseases, Bacterial; Soft Tissue Infections; Vancomycin

Skin and soft tissue infections, such as cellulitis, are commonly diagnosed in the emergency department and these patients are often admitted to the hospital for intravenous antibiotic therapy. Oritavancin is a novel antibiotic approved for the treatment of skin and soft tissue infections that is administered as a one-time infusion. While oritavancin has demonstrated comparable efficacy with multi-dose parenteral antibiotics in clinical trials and has been proposed as an alternative to admission for emergency department patients, there is a paucity of available real world effectiveness data. In this case series, we describe the characteristics and outcomes of ten patients with high-risk skin and soft tissue infections who received oritavancin and were discharged from the emergency department.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cellulitis; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Lipoglycopeptides; Male; Middle Aged; Retrospective Studies; Soft Tissue Infections

To assess oritavancin activity in vitro against clinically relevant Gram-positive pathogens causing skin and soft-tissue infections (SSTIs) in European and US hospitals.. 13 262 consecutive and unique isolates deemed to be responsible for SSTIs were included. Isolates originated from 36 and 27 institutions in Europe (Israel included) and the USA, respectively, between 2010 and 2013.. Oritavancin (98.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.03, 0.03 and 0.06 mg/L, respectively, for Staphylococcus aureus. CoNS from the USA (MIC50, 0.015 mg/L) demonstrated an MIC50 value of oritavancin slightly lower than those from Europe (MIC50, 0.03 mg/L). Overall, vancomycin-resistant (VanA-phenotype) Enterococcus faecalis had oritavancin MICs (MIC50/90, 0.25/0.5 mg/L) that were 16-fold higher than those obtained for vancomycin-susceptible isolates (MIC50/90, 0.015/0.03 mg/L; 99.2%-99.8% susceptible); nevertheless, oritavancin inhibited all VanA E. faecalis at ≤0.5 mg/L. Equivalent oritavancin MICs (MIC50/90, 0.004/0.008 mg/L) were noted for all VanB and vancomycin-susceptible Enterococcus faecium, while higher MICs (MIC50/90, 0.03/0.12 mg/L) were obtained for VanA strains. Oritavancin had low MICs against the overall populations of Streptococcus pyogenes (MIC50/90, 0.03/0.12 mg/L; 98.4%-98.6% susceptible), Streptococcus agalactiae (MIC50/90, 0.03/0.06 mg/L; 97.9%-98.0% susceptible) and the Streptococcus anginosus group (MIC50/90, 0.008/0.015 mg/L; 100.0% susceptible), with slightly higher MICs for Streptococcus dysgalactiae (MIC50/90, 0.06/0.25 mg/L; ≥98.3% susceptible).. Oritavancin had potent activity in vitro against this contemporary collection of European and US isolates causing SSTIs. These results describe oritavancin activity against Gram-positive pathogens collected shortly prior to its regulatory approval in the USA.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Europe; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lipoglycopeptides; Microbial Sensitivity Tests; Public Health Surveillance; Skin Diseases, Bacterial; Soft Tissue Infections; United States